The Operations, Clinical Assessment and Administrative Core oversees this entire project and is responsible for the conduct of the clinical trial and the collection of biological and behavioral data. Based on studies of groups of major depressive disorder (MDD) patients, any single psychotherapeutic or pharmacological strategy in clinical practice today achieves remission in only a minority of patients. Thus the initial treatment an individual with MDD receives is largely an accident of chance rather than an evidence based choice. Over a 5-year period, 400 treatment naive patients with MDD will be recruited into a 12 week treatment trial of randomly assigned treatment with an SSRI, escitalopram, a dual 5-HT/NE re-uptake inhibitor, duloxetine or cognitivebehavior therapy (CBT). Subjects will be evaluated using state-of-the-art clinical assessments prior to, during and at the end of acute treatment period. This core describes the efforts that will result in the identification, recruitment of the patients, and assessment and delivery of the treatments. A unique component of this proposal is the study of individuals with MDD not contaminated by previous treatments that may confound measures of treatment response. Commensurate with the CIDAR goals, the data generated in this core will provide the critical foundation for hypothesis generation and testing in the other cores and projects.